A new twist in the hairpin

Researchers from the Whitehead Institute last week published in Sciencetheir design of 5-Helix, a protein that inhibits HIV-1 entry into cells by binding gp41, an envelope protein crucial to membrane fusion. The design of 5-Helix represents a new way to use gp41 as a target for HIV therapeutics, using a methodology that potentially could be extended to inhibit membrane fusion of a variety of viruses.

It has long been known that during HIV-1 membrane fusion, gp41 interacts with the target cell and then loops so that three alpha helices on the amino (NH2) terminal end of the protein bind three alpha helices on the carboxyl (COOH) terminal end. The conformation is known as the trimer-of-hairpins. The trimer-of-hairpins structure is a mechanism that is used by numerous viruses including influenza, Ebola, and respiratory syncytial virus (RSV) to enter mammalian cells...